Even in its most common form, childhood cancer is rare. Imagine then that the reason your 2-year-old daughter is vomiting and can’t hold her head straight is not a virus, as doctors originally suspected, but an incredibly rare brain tumor. This is precisely what John Savage and Michelle Long of Cork, Ireland, faced in November 2012, when their daughter Alisha Savage was diagnosed with Stage IV atypical teratoid rhabdoid tumors.

On Jan. 24, 2014, the family arrived in Boston to have Alisha treated at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “We researched a lot of hospitals in the U.S. We didn’t just jump on a plane. This is our best hope,” John Savage says. “We could be here three months. It could be three years.”

The Boston Herald’s coverage of Alisha’s story is drawing attention to her plight and the importance of research into rare childhood cancers. Indeed, gene mutations present in AT/RT and other cancers in very young children and often provide fundamental insights into cancer in general.

Atypical teratoid rhabdoid tumors (AT/RT) are aggressive tumors of the central nervous system that usually occur in the brain’s cerebellum, which controls movement and balance, and in the brain stem, which controls basic bodily functions. The tumors appear most often in children under age 3; the survival rate is 40 to 45 percent. The disease is so rare that even a major center like Dana-Farber/Boston Children’s sees only about five new cases per year. Now plans are underway to create a registry to track patients with AT/RT.

The search goes global

Alisha was treated in Dublin with surgery, followed by chemotherapy and radiation. When cancer was detected in her spine in July 2013, she received another round of radiation. Meanwhile, her parents were scouring the Internet for information. When they typed in “atypical teratoid rhabdoid tumor,” two names kept popping up: Mark Kieran, MD, PhD, clinical director of the Brain Tumor Center at Dana-Farber/Boston Children’s, and his colleague Susan Chi, MD.

Alisha. Photo by Sam Ogden

“Any angle you take, it always came back to Drs. Kieran and Chi,” Savage says. “It blew us out of the water. There’s actually a hospital dealing with what Alisha has.”

AT/RT was not recognized as a separate disease until the late 1980s and 1990s, with the discovery of a mutated gene that distinguishes it from medulloblastoma and primitive neuroectodermal tumors. Until 2000, all brain tumor patients under 3 years received the same treatment. That changed when Kieran and Chi developed a specific protocol for AT/RT, which the Journal of Clinical Oncology published in 2009.

Dana-Farber/Boston Children’s scientist Charles Roberts, MD, PhD, conducts research into AT/RT. In 2000,he showed that the mutated gene (SMARCB1) associated with AT/RT does, in fact, cause cancer. It is also part of a cellular complex implicated in 20 percent of all cancers. “Understanding AT/RT,” Roberts says, “potentially has implications for patients with many, many types of cancer.”

In 2012, Roberts’ lab discovered that SMARCB1 is the only mutation involved in AT/RT, thus focusing scientists’ search for potential treatment targets. Efforts by the Roberts lab have led to a Phase I clinical trial for children with AT/RT of a Novartis drug that is also being tested in adults with some forms of leukemia and solid tumors.

“We’ve got a great researcher who does the preclinical work,” Chi says, “and like a baton, it gets handed to the next phase, a clinical trial that we hope leads to improved outcomes.

Meanwhile, after tests in Boston indicated that the most recent radiation may have slowed the disease’s progression, Alisha has started a new round of outpatient chemotherapy.

In Ireland, Savage owned an auto garage, and Long, who was seven months pregnant with their second child when Alisha was diagnosed, was a stay-at-home mother. Savage had to close his business. “It wasn’t a choice,” he says. “It was Alisha or the garage. We knew the answer to that.” The other day they arrived at Dana-Farber/Boston Children’s Jimmy Fund Clinic pushing Alisha in one stroller and 1-year-old Emma in another.

The family is staying in the Hanover home of Kenneth Smith and Laura MacConaill, PhD. Smith is a distant relation whom Savage learned of while making plans to come to Boston. In a striking coincidence, MacConaill is scientific director of Dana-Farber’s Center for Cancer Genome Discovery and has participated in AT/RT research with Kieran, Roberts and Chi.

“We had to give Alisha a chance,” Savage says. “We know there’s not a cure, but any new treatments will come through here.”